All About Small Cell Lung Cancer

OncoLink
The University of Pennsylvania Medical School
Last Modified: December 17, 2013

What are the lungs?

The lungs are two spongy organs found in the chest. They are responsible for delivering oxygen to the bloodstream. When you take a breath in, air moves into the lungs causing them to expand. The air can then come very close to blood that is traveling in small vessels called capillaries. When you breathe out, you exhale substances that you don't need, like carbon dioxide. The lungs are specially designed to place blood in close contact with as much air as possible, so their tissues are very delicate. The right lung has three sections, which are called lobes; the left lung has two lobes. Air comes in through your mouth and nose and then travels down a tube, called the trachea, to the lungs. The trachea divides into smaller branches called bronchi, and the bronchi keep dividing and dividing like branches on a tree. As the branches get smaller, they are called bronchioles. At the end of the branches, there are little sacs of air called alveoli. The air comes into contact with blood in the alveoli. The lungs are exposed to whatever you breathe in, so any toxic chemicals or pollutants in the air you breathe can get into your body through your lungs.

What is lung cancer?

Lung cancer happens when cells in the lung begin to grow out of control and can then invade nearby tissues or spread throughout the body. Large collections of cancer cells are called tumors. Cells in any of the tissues in the lung can develop cancer; but most commonly, lung cancer comes from the lining of the bronchi. Lung cancer is not really thought of as a single disease, but rather a collection of several diseases that are characterized by the cell type that makes them up, how they behave, and how they are treated. Lung cancer is divided into two main categories:

Small cell lung cancer (SCLC) - the rarer of the two types (about 15% of all lung cancers), small cell lung cancer is more aggressive than non-small cell lung cancer because it grows more quickly and is more likely to spread to other organs.

Non-small cell lung cancer (NSCLC) - the more common of the two types (85% of all lung cancers), non-small cell lung cancer is generally slower growing than small cell lung cancer and is divided into different types based on how the cells look that make it up - adenocarcinoma, squamous cell carcinoma, and poorly differentiated or large cell carcinoma.

Am I at risk for lung cancer?

Lung cancer is the most common cause of cancer death worldwide for both men and women, with an estimated 1.6 million new cases and 1.4 million deaths annually. In the United States alone, it is estimated that 228,190 people will be diagnosed and 159,480 people will die from lung cancer in 2013. In comparison, 120,580 people are expected to die from colon, breast and prostate cancer combined in 2013 (the 2nd, 3rd, and 4th most common cancers in the U.S.).

In the US, the number of women getting lung cancer rose dramatically in the 1980s; this was attributed to the increase in women smoking some 30+ years earlier. Lung cancer due to smoking has about a 20-year latency period- that is the time from when the person starts smoking until a cancer develops. In the 1990s, lung cancer overtook breast cancer as the most common cause of cancer death among women. Almost twice as many women are expected to die from lung cancer as compared to breast cancer in the US. The good news is these rates have been declining since the early 2000s, reflecting the decline in tobacco use and has been seen in the US and Europe.

Smoking and Lung Cancer Risk

While there are a few potential causes of lung cancer, by far the most common is smoking tobacco. Every smoker (current or former) is at risk for lung cancer. It is estimated that 80-90% of all cases of lung cancer are caused by cigarette smoking, with small cell lung cancer occurring almost exclusively in people with a smoking history. Your risk of getting lung cancer from cigarette smoking increases the longer you smoke, the more you smoke, and the deeper you inhale. Smoking low tar cigarettes does not prevent you from getting lung cancer. Importantly, if you quit smoking, your risk of getting lung cancer declines. The longer you go without smoking, the greater your risk declines. It is never too late to quit because your risk declines no matter how long you have been smoking.

What if you have already been diagnosed with a lung cancer? Approximately 50% of people diagnosed with lung cancer are active smokers. Patients who have been diagnosed with lung cancer have been found to respond to treatment better and live longer if they quit smoking at the time of their diagnosis. They can have more difficulty getting through treatment, being at higher risk of side effects such as pneumonia and lung inflammation, which can result in needing to lower the chemotherapy doses a person receives, resulting in less effective therapy. In addition, having given up smoking decreases the chance of developing another lung cancer after treatment for the current cancer.

Smoking also has an affect on people around you. Second-hand smoke, or smoke inhaled when you are near someone smoking, is another risk factor for lung cancer. It is estimated that approximately 15% of cases of lung cancer in non-smokers are caused by second-hand smoke exposure in childhood and adolescence. Non-smoking spouses of smokers are 30% more likely than spouses of non-smokers to get lung cancer. Even though many people don't "inhale" them, smoking pipes and cigars is a risk factor for lung cancer as well. Even though you are not inhaling, you are breathing the air that is filled with the smoke from these products. The more pipes or cigars you smoke, the more likely you are to get lung cancer. Although it is not as well established as cigarette smoking, smoking marijuana is also a risk factor for getting lung cancer. Both the magnitude and duration of marijuana use seems to be related to your overall risk.

Radon

Radon is the second leading cause of lung cancer in the United States. Radon is a naturally occurring odorless, colorless radioactive gas that results from the decay of rock and soil components. Radon moves up from the ground into homes, where it becomes trapped and accumulates, exposing the inhabitants to its cancer-causing potential. Different areas of the world have different amounts of radon produced, but the type of foundation in your home is also important, since some foundations are better ventilated. Because of this, two homes next door to each other could have different levels of radon in the indoor air.

Radon can accumulate in new and old homes and those with OR without a basement. The only way to know if your home contains radon is to have it tested, which can be done using a kit from a hardware store or having a radon professional perform the test. Many areas have laws requiring radon testing before a house is sold. If radon is detected in levels above 4 pCi/L (picocuries per liter), you can have a removal system installed, which vents the gas to the outside using a pipe and fan system. Because it is not clear what level of radon is safe, the EPA recommends that people consider a removal system for levels from 2-4 pCi/L.

Radiation Exposure

Radiation therapy for a prior cancer that includes lung tissue in the treatment field increases the risk for developing a new cancer in that area of the lung. Such secondary cancers often take a decade or longer to develop. This can be seen in people treated for Hodgkin lymphoma and breast cancer, among others. Some guidelines suggest that Hodgkin lymphoma survivors have screening for lung cancers after treatment. Modern radiation equipment and planning reduce the exposure of healthy tissue and may reduce this risk.

Other Risk Factors

Although smoking cigarettes is by far the most common and important risk factor for getting lung cancer, there are some environmental exposures that increase your risk for lung cancer as well. People who work with asbestos are more likely to get lung cancer; and if they smoke cigarettes too, their risk rises even higher. Asbestos is found in industries like shipbuilding, insulation/fireproofing, and asbestos mining and production. Other workers who may have a higher risk of lung cancer are those exposed to arsenic, chromium, nickel, vinyl chloride, hard metal dusts, talc, uranium, and gasoline and diesel exhaust fumes.

People who have already had lung cancer are at risk for getting it again. A history of interstitial lung disease, pulmonary fibrosis or tuberculosis (TB) also increases your risk of getting lung cancer. However, it should be stressed that cigarette smoking is far and away the most important and dangerous risk factor for developing lung cancer.

How can I prevent lung cancer?

The best way to prevent lung cancer is to quit smoking, or to never start in the first place. Avoid being around people who are smoking and do not use pipes, cigars, and marijuana. Have your home tested for radon and install a removal system if needed. If you work in an industry where you are exposed to substances known to cause lung cancer, make sure to use all the proper protective equipment and attire made available by your employer.

There has been some suggestion that a diet high in fruits and vegetables may decrease your risk of lung cancer. This has yet to be definitively proven. Many substances, including antioxidants like vitamin A, vitamin E, and beta-carotene, have been suggested to decrease your risk of lung cancer. None of these has been shown to be beneficial in randomized controlled trials and are not recommended for this purpose. In fact, large clinical trials have shown an increased risk of lung cancer among smokers that take high doses of vitamin E, vitamin A, and beta-carotene in the form of supplements.

The future of lung cancer prevention will rely on sophisticated analysis of patients' genes and molecular markers for lung cancer risk; this coupled with "smart drug" design and novel imaging techniques may one day help decrease the risk of developing lung cancer. Though a tremendous first step would be to get to a world of non-smokers.

What screening tests are available?

Many studies were done comparing people who were screened with chest x-rays andor sputum samples, but they never found a decrease in deaths from lung cancer as a result of this screening. However, this issue was hotly debated because some studies found that cancers can be picked up in earlier stages if patients are screened with chest x-rays. The problem is that picking up the cancers earlier did not translate to a decrease in deaths because of the screening.

The National Lung Screening Trial began in 2002 and was designed to compare annual chest CT scans (a low dose spiral CT) to chest x-rays to screen high-risk patients, with the goal of improving survival by detecting lung cancer earlier. The study had 53,000 participants who were between the ages of 55 and 74 and were current or former heavy smokers, which was defined as a minimum of 30 pack year history (pack years = # of packs per day x # of years smoked). The study found that CT scan found significantly more cancerous and pre-cancerous lesions than chest x-ray. In addition, this translated into a 20% reduction in the number of deaths from lung cancer. People screened with CT scans had more areas of concern detected, which means more testing that may ultimately not turn out to be cancer (called a false positive), but experts agree that the benefits of screening in this high risk population outweigh the risks. In 2013, the US Preventive Task Force recommended annual CT screening in current or former (quit in the last 15 years) heavy smokers, ages 55-79, taking into consideration their health and ability to undergo curative surgery if a cancer is found.

What are the signs of lung cancer?

Unfortunately, the early stages of lung cancer may not have any symptoms. As the tumor grows in size, it can produce a variety of symptoms including:

Cough (especially one that doesn't go away or gets worse in character)

Chest pain

Shortness of breath

Coughing up blood or bloody phlegm

New onset hoarseness or wheezing

Recurrent problems with pneumonia or bronchitis

Weight loss

Loss of appetite

Fatigue

Bone pain

Dizziness or double vision

Hoarseness of change in speech

Numbness or tingling in your arms or legs

Arm pain or weakness

Neck or facial swelling

Yellowing of the skin or whites of the eyes (jaundice)

Seizures

Many of these symptoms are non-specific, and could represent a variety of different conditions; however, your doctor needs to see you if you have any of these problems. Most patients (approximately 85%) who are diagnosed with lung cancer have symptoms that prompt a doctor to order tests to look for a problem. A cough is the most common presenting symptom of lung cancer; however, many long-term smokers have a chronic cough, so it is especially important for someone with a chronic cough to see their doctor if their cough changes in character or severity.

How is lung cancer diagnosed and staged?

When someone has symptoms suggestive of a lung tumor, they will typically be referred for blood work and a chest x-ray and/or CT scan (a 3-D x-ray) of the chest to better characterize the lesion. Your doctor may order sputum cytology, which means examining your phlegm for cancer cells. To see if the lung cancer has spread outside of the chest, you likely will also undergo a CT scan of the abdomen and/or a PET-CT scan. To see if the lung cancer has spread specifically to the brain, you will be referred for an MRI scan or CT scan of the brain.

While all of these tests are important pieces of the puzzle, a biopsy is the only way to know for sure if you have cancer. A biopsy takes a sample of the suspicious area, which is then examined under a microscope for the presence of cancer cells. In addition, the biopsy is necessary to determine the type of lung cancer and if there are cancer cells present in the lymph nodes.

Biopsy

A biopsy may be taken of the suspicious nodule in the lung and/or from lymph nodes near the lungs. Your doctor will determine which areas should be biopsied and which biopsy method is best in your case. Biopsies are often done by a lung surgeon or a pulmonologist (a doctor specializing in lung diseases) who is trained in brochoscopy. Possible methods for obtaining a biopsy include:

Bronchoscopy: uses a thin, lighted tube placed down your nose or mouth and into your lung to look at the tumor and take samples of it. This can also be used to take samples of the lymph nodes. There are several brochoscopy techniques that can be used; your doctor will determine which methods are best in your case based on the location of the lesion and if lymph nodes are being sampled.

Needle biopsy: a needle is placed through the skin and between the ribs, into the tumor to get cells.

Thoracoscopy: A surgical procedure where the surgeon inserts a small camera into the chest wall to look at the suspicious area, evaluate the extent of it and take biopsies.

Video-assisted thoracoscopy or VATS: can be used for a biopsy or surgery in early stage lung cancer; this technique is similar to thoracoscopy but requires fewer/smaller incisions, which may result in quicker recovery.

Mediastinoscopy: A surgical procedure that uses a scope (camera on a tube), placed through the chest wall, to look at the suspicious area and take samples of lymph nodes to evaluate for the presence of cancer cells.

In some cases, tumors cells can get into the fluid around your lungs (called pleural fluid), and your doctor may want to drain off some fluid by putting a needle into the space where the fluid is (called a thoracentesis) and examine that fluid under a microscope.

Pathology

Once the tissue is removed, a doctor called a pathologist examines the specimen under a microscope. The pathologist determines if it is cancer or not; and if it is cancerous, they will characterize it by what type of tissue it arose from, what subtype of lung cancer it is, how abnormal it looks (known as the grade), and whether or not it is invading surrounding tissues or lymph nodes. The pathologist sends a pathology report to your doctor, detailing his/her findings, which is an important piece in planning your treatment. You can request a copy of your report for your records.

Staging

In order to guide treatment and offer some insight into prognosis, lung cancer is "staged." This stage is based on the size and location of the tumor, if there are cancer cells in the lymph nodes and if there are cancer cells found in other areas of the body.

The staging system is different for the two main types of lung cancer: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). While SCLC is increasingly being staged using the "TNM" staging system that is the same system being used for NSCLC (and many other cancer types), many providers that treat small cell lung cancer commonly divided the staging into just two stages:

Limited Stage - means the cancer is on only one side of the chest (lung and/or lymph nodes), and could be reasonably treated with a single radiation therapy field.

Extended Stage - means the cancer is on both sides of the chest (spread to both lungs and/or lymph nodes on both sides of the body) or spread outside of the chest to other areas of the body, so it could not be reasonably treated with one radiation therapy field.

Your doctors will want to know the stage of your cancer before treatment is planned, because the stage of the cancer drastically affects how it is treated. Part of your workup is done to look for spread of the tumor (metastasis) and will probably include CT scans of the liver and adrenal glands (located above the kidneys), a CT scan or MRI (a scan that uses magnets instead of radiation) of your brain, and a PET scan. If you are having particular symptoms, your provider may want different or more specific exams to determine their cause. Overall, your providers will want to know as much about your cancer as possible so that they can plan the best available treatments.

What are the treatments for lung cancer?

The treatments vary quite a bit for non-small cell and small cell lung cancers. The following discussion addresses the treatment of small cell lung cancers.

Surgery

For many types of cancer, including NSCLC, surgery is an important part of treatment. This has historically not been true for SCLC. Most patients with this disease have lymph node involvement or distant metastases at the time of diagnosis. Surgery is a "local" treatment, meaning it only treats the area removed during the surgery. When cancer cells have already spread to areas outside of the lung, it is necessary to treat with a "systemic" therapy, in other words, one that can reach all areas of the body, such as chemotherapy. A few clinical trials have compared surgery (with or without other treatments) to treatment with chemotherapy and radiation therapy, though none have found a benefit in survival for those who underwent surgery.

The one exception to this is very early stage SCLC, where there is no cancer found in lymph nodes. In these rare cases, surgery to remove the lobe of the lung containing the tumor, combined with other therapies like chemotherapy, is the preferred treatment for patients who can tolerate this surgical procedure.

Treatment For Limited Stage (LS-SCLC) Disease

SCLC is very sensitive to chemotherapy and the majority of patients treated with chemotherapy will have a good response to initial treatment. Chemotherapy for limited stage disease is often combined with radiation therapy, and this combination has been shown to improve survival over chemotherapy alone. Unfortunately, most patients will ultimately develop resistance to chemotherapy and experience disease progression.

The chemotherapy given is most often a combination of a "platinum" medication (cisplatin or carboplatin) combined with etoposide, which is generally given in your doctor's office or infusion center for 3 days in a row, followed by 18-25 days "off." This 21-28 days is called a "cycle" and most patients will receive 4 to 6 cycles. This regimen is most often given in combination with radiation therapy, which can be given once daily or twice (also called hyperfractionated) daily. If given once a day, radiation therapy is typically administered over 6 to 8 weeks, and if given twice daily, is administered over 3 weeks. Radiation therapy is preferably given during the same time period as chemotherapy is being given, and it is optimally started as early after diagnosis as is feasible. However, in some cases, it may be preferable to give the radiation therapy after the chemotherapy is completed.

After finishing this treatment, patients who are doing well, have had a good response to the treatment, and the disease has not spread anywhere outside of the chest, may be offered treatment with "PCI" or prophylactic cranial irradiation. SCLC tends to spread to the brain, despite treatment with chemotherapy. Studies have found that patients treated with radiation therapy to the whole brain after completing induction chemotherapy have reduced rates of brain metastases and improved survival rates.

Treatment for Extensive Stage (ES-SCLC) Disease

As with limited stage disease, SCLC is very sensitive to chemotherapy and the majority of patients treated with chemotherapy will have a good response to initial treatment. Unfortunately, most patients will ultimately develop resistance to chemotherapy and experience disease progression.

The chemotherapy given is most often a combination of a "platinum" medication (cisplatin or carboplatin) combined with etoposide or irinotecan, which is generally given in your doctor's office or infusion center for 3 days in a row, followed by 18-25 days "off." This 21-28 days is called a "cycle" and most patients will receive 4 to 6 cycles. Some patients may benefit from receiving "consolidation radiation" to the chest, which is given after completing chemotherapy to some patients who had a good response to chemotherapy.

After finishing this treatment, patients who are doing well, have had a good response to the treatment, and the disease has not spread anywhere outside of the chest may be offered treatment with "PCI" or prophylactic cranial irradiation. SCLC tends to spread to the brain, despite treatment with chemotherapy. Studies have found that patients treated with radiation therapy to the whole brain after completing induction chemotherapy have reduced rates of brain metastases and improved survival rates. Patients who have been found to have the cancer spread to the brain can also benefit from radiation therapy to the brain, with improved survival and quality of life.

Follow-up After Treatment

Once a patient has been treated for lung cancer, he or she needs to be closely followed for a recurrence. At first, you will have follow-up visits fairly often. The longer you are free of disease, the less often you will have to go for checkups. Your healthcare provider will tell you when he or she wants follow-up chest x-rays, CT scans, or other tests. Small cell lung cancer is considered an aggressive tumor that often comes back after treatment; thus it is very important that you let your doctor know about any symptoms you are experiencing and that you keep all of your follow-up appointments.

Finally, if you haven't yet done it, you need to quit smoking. It is never too late to get the health benefits of smoking cessation, even after a cancer diagnosis. If your family members smoke, it is a great opportunity to support each other and quit together. There are many programs to provide support in quitting and good medications to support your efforts as well. Learn more about smoking cessation on OncoLink.

Clinical trials are extremely important in furthering our knowledge and the treatment of this disease. It is though clinical trials that we know what we do today, and exciting new therapies are always being tested. Talk to your healthcare provider about participating in clinical trials in your area or search for trials using the OncoLink Clinical Trials Matching program.

Cancer survivorship is a relatively new focus of oncology care. With some 13 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a care plan today on OncoLink.

This article is meant to give you a better understanding of lung cancer. You may find this knowledge useful when meeting with your physician, making treatment decisions, and continuing your search for information.